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Phenotype Ontology
Like Gene Ontology (GO), phenotypy ontology classifies and organizes gene-mutant/null phenotypic information from the very general at the top to more specific terms in the directed acyclic graph (DAG) by viewing an individual term as a node and its relations to parental terms (allowing for multiple parents) as directed edges. To navigate this hierarchy, we display all parental phenotypic terms to the current phenotypic term of interest ordered by their shortest distances to the current term. Also, only direct children phenotypic terms of the current phenotypic term are listed. Phenotype ontologies we have incorporated are as follows:

• Disease Ontology (DO) Ontology (DO)
  DO semantically integrates disease and medical vocabularies through extensive cross mapping of DO terms to MeSH, ICD, NCI thesaurus, SNOMED and OMIM.
  
• Human Phenotype (HP) Ontology (HP)
  HP captures phenotypic abnormalities that are described in OMIM, along with the corresponding disease-causing genes. It includes three complementary biological concepts: Mode_of_Inheritance (MI), ONset_and_clinical_course (ON), and Phenotypic_Abnormality (PA).
  
• Mouse Phenotype (MP) Ontology (MP)
  MP describes phenotypes of the mouse after a specific gene is genetically disrupted. Using it, Mouse Genome Informatics (MGI) provides high-coverate gene-level phenotypes for the mouse.
  
• Worm Phenotype (WP) Ontology (WP)
  WP classifies and organizes phenotype descriptions for C. elegans and other nematodes. Using it, WormBase provides primary resource for phenotype annotations for C. elegans.
  
• Yeast Phenotype (YP) Ontology (YP)
  Based on YP which is the major contributor to the Ascomycete phenotype ontology, Saccharomyces Genome Database (SGD) provides single mutant phenotypes for every gene in the yeast genome.
  
• Fly Phenotype (FP) Ontology (FP)
  FP refers to FlyBase controlled vocabulary. Specifically, a structured controlled vocabulary is used for the annotation of alleles (for their mutagen etc) in FlyBase.
  
• Fly Anatomy (FA) Ontology (FA)
  FA is a structured controlled vocabulary of the anatomy of Drosophila melanogaster, used for the description of phenotypes and where a gene is expressed.
  
• Zebrafish Anatomy (ZA) Ontology (ZA)
  ZA displays anatomical terms of the zebrafish using standard anatomical nomenclature, together with affected genes.
  
• Xenopus Anatomy (XA) Ontology (XA)
  XA represents the lineage of tissues and the timing of development for frogs (Xenopus laevis and Xenopus tropicalis). It is used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes.
  
• Arabidopsis Plant Ontology (AP) Ontology (AP)
  As a major contributor to Plant Ontology which describes plant anatomical and morphological structures (AN) and growth and developmental stages (DE), the Arabidopsis Information Resource (TAIR) provides arabidopsis plant ontology annotations for the model higher plant Arabidopsis thaliana.
  
• Enzyme Commission (EC) Ontology (EC)
  Each enzyme is allocated a four-digit EC number, the first three digits of which define the reaction catalysed and the fourth of which is a unique identifier (serial number). Each enzyme is also assigned a systematic name that uniquely defines the reaction catalysed.
  
• DrugBank ATC (DB) Ontology (DB)
  In the Anatomical Therapeutic Chemical (ATC) classification system, drugs are classified in groups at five different levels according to the organ or system (1st level, anatomical main group) on which they act and their therapeutic (2nd level, therapeutic subgroup), pharmacological (3rd level, pharmacological subgroup) and chemical properties (4th level, chemical subgroup; 5th level, chemical substance). Only drugs in DrugBank are considered.
  
• UniProtKB KeyWords (KW) Ontology (KW)
  Keywords in UniProtKB are controlled vocabulary, providing a summary of the entry content and are used to index UniProtKB/Swiss-Prot entries based on 10 categories (the category "Technical term" being excluded here). Each keyword is attributed manually to UniProtKB/Swiss-Prot entries and automatically to UniProtKB/TrEMBL entries (according to specific annotation rules).
  
• UniProtKB UniPathway (UP) Ontology (UP)
  UP is a fully manually curated resource for the representation and annotation of metabolic pathways, being used as controlled vocabulary for pathway annotation in UniProtKB.
  

Structural Domain Phenotype Ontology and its Annotations
Structural Classification of Proteins (SCOP) classifies evolutionary-related domains into Superfamily level and Family level. Using the phenotype ontologies above, we have generated the domain-centric phenotype annotations, and further identified those phenotype terms which are the most informative to annotate SCOP domains. Promisingly, domain-centric phenotypic annotations can serve as an alternative starting point to explore genotype-phenotype relationships. We provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Structural Domain Disease Ontology (DO) Ontology (SDDO) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DO.txt, and the corresponding ontology:SDDO.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Human Phenotype (HP) Ontology (SDHP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2HP.txt, and the corresponding ontology:SDHP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Mouse Phenotype (MP) Ontology (SDMP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2MP.txt, and the corresponding ontology:SDMP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Worm Phenotype (WP) Ontology (SDWP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2WP.txt, and the corresponding ontology:SDWP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Yeast Phenotype (YP) Ontology (SDYP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2YP.txt, and the corresponding ontology:SDYP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Phenotype (FP) Ontology (SDFP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FP.txt, and the corresponding ontology:SDFP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Anatomy (FA) Ontology (SDFA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FA.txt, and the corresponding ontology:SDFA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Zebrafish Anatomy (ZA) Ontology (SDZA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2ZA.txt, and the corresponding ontology:SDZA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Xenopus Anatomy (XA) Ontology (SDXA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2XA.txt, and the corresponding ontology:SDXA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Arabidopsis Plant Ontology (AP) Ontology (SDAP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2AP.txt, and the corresponding ontology:SDAP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Enzyme Commission (EC) Ontology (SDEC) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2EC.txt, and the corresponding ontology:SDEC.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain DrugBank ATC (DB) Ontology (SDDB) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DB.txt, and the corresponding ontology:SDDB.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB KeyWords (KW) Ontology (SDKW) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2KW.txt, and the corresponding ontology:SDKW.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB UniPathway (UP) Ontology (SDUP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2UP.txt, and the corresponding ontology:SDUP.txt) and mysql tables (Domain2PO.sql.gz).
  

Supra-domain Phenotype Ontology and its Annotations
Although domain-centric annotations hold great promise in describing phenotypic nature of independent domains, most domains themselves may not just work alone. In multi-domain proteins, they may be combined together to form distinct domain architectures. The recombination of the existing domains is considered as one of major driving forces for phenotypic diversificaation. As an extension, we have also generated supra-domain phenotype ontology and its annotations. Compared to domain-centric phenotype ontology and annotations (SCOP domains at the Superfamily level and Family level), this version focuses on supra-domains and individual SCOP domains ONLY at the Superfamily level. Besides, in terms of individual superfamilies, their annotations from the domain-centric version may be different from those from supra-domains version. Depending on your focus, the former should be used for the consideration of both the Superfamily level and Family level, otherwise the latter should be used if you are interested in domain combinations. Also, we provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Supra-domain Domain Disease Ontology (DO) Ontology (SPDO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DO.txt, and the corresponding ontology:SPDO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Human Phenotype (HP) Ontology (SPHO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2HP.txt, and the corresponding ontology:SPHO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Mouse Phenotype (MP) Ontology (SPMP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2MP.txt, and the corresponding ontology:SPMP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Worm Phenotype (WP) Ontology (SPWP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2WP.txt, and the corresponding ontology:SPWP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Yeast Phenotype (YP) Ontology (SPYP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2YP.txt, and the corresponding ontology:SPYP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Phenotype (FP) Ontology (SPFP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FP.txt, and the corresponding ontology:SPFP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Anatomy (FA) Ontology (SPFA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FA.txt, and the corresponding ontology:SPFA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Zebrafish Anatomy (ZA) Ontology (SPZA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2ZA.txt, and the corresponding ontology:SPZA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Xenopus Anatomy (XA) Ontology (SPXA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2XA.txt, and the corresponding ontology:SPXA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Arabidopsis Plant Ontology (AP) Ontology (SPAP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2AP.txt, and the corresponding ontology:SPAP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Enzyme Commission (EC) Ontology (SPEC) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2EC.txt, and the corresponding ontology:SPEC.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain DrugBank ATC (DB) Ontology (SPDB) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DB.txt, and the corresponding ontology:SPDB.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB KeyWords (KW) Ontology (SPKW) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2KW.txt, and the corresponding ontology:SPKW.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB UniPathway (UP) Ontology (SPUP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2UP.txt, and the corresponding ontology:SPUP.txt) and mysql tables (SP2PO.sql.gz).
  

Superfamily domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
Orange domain-like	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
L27 domain	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
MIR domain	0	DIRECT
Mob1/phocein	0	DIRECT
ARID-like	0	DIRECT
Integrin domains	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
PurM N-terminal domain-like	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
Second domain of FERM	0	DIRECT
Serpins	0	DIRECT
PreATP-grasp domain	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
TIMP-like	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
cAMP-binding domain-like	0	DIRECT
Smc hinge domain	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
Cytokine	0	DIRECT
SMAD MH1 domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
PurM C-terminal domain-like	0	DIRECT
Rhomboid-like	0	DIRECT
Thiamin diphosphate-binding fold (THDP-binding)	0	DIRECT
PX domain	0	DIRECT
RCC1/BLIP-II	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Putative DNA-binding domain	0	DIRECT
Sema domain	0	DIRECT
SAP domain	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Plexin repeat	0	DIRECT
SAICAR synthase-like	0	DIRECT
Homeodomain-like	0.0000000002065	DIRECT
beta-beta-alpha zinc fingers	0.000005191	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.000006068	DIRECT
Fibronectin type III	0.000642	DIRECT
Immunoglobulin	0.003484	INHERITED FROM: abdominal nerve || synaptic neuropil || commissure || leg taste bristle chemosensory neuron || embryonic/larval peripheral nervous system || abdominal segmental nerve || antennal lobe glomerulus || connective || nerve || LNv neuron || LN period neuron || interface glial cell || tract neuropil || neuropil glial sheath
Protein kinase-like (PK-like)	0.005409	INHERITED FROM: synaptic neuropil || intestinal stem cell || adult midgut epithelium
Nuclear receptor ligand-binding domain	0.01055	INHERITED FROM: synaptic neuropil || central brain || protocerebrum || mushroom body gamma-lobe || supraesophageal ganglion neuron || neuropil || synaptic neuropil block
p53-like transcription factors	0.01055	INHERITED FROM: mesothoracic tergum || adult external thorax
Glucocorticoid receptor-like (DNA-binding domain)	0.01066	INHERITED FROM: region of integument || adult external thorax
SH2 domain	0.01095	INHERITED FROM: wing blade || ommatidium || adult peripheral nervous system || connective || midline crossing tract || photoreceptor cell R7
PH domain-like	0.0331	INHERITED FROM: embryonic foregut
HMG-box	0.04311	INHERITED FROM: wing || adult external thorax
Cystine-knot cytokines	0.07051	INHERITED FROM: stigmatophore || embryonic/larval spiracle || embryonic/larval posterior spiracle
EGF/Laminin	0.1042	INHERITED FROM: proventriculus || tendon cell || wing blade || eye photoreceptor cell stalk || embryonic/larval midgut cell || larval caeca region || ocellus || ventral nervous system || adult midgut progenitor cell
Ankyrin repeat	0.1139	INHERITED FROM: Johnston organ neuron
Toll/Interleukin receptor TIR domain	0.1977	INHERITED FROM: ventral nerve cord
Snake toxin-like	0.1977	INHERITED FROM: embryonic/larval neuromuscular junction || wing vein || wing cell
Transducin (alpha subunit), insertion domain	0.1977	INHERITED FROM: eo neuron
Growth factor receptor domain	0.2598	INHERITED FROM: RP2sib neuron || proventriculus || embryonic/larval midline of ventral nerve cord || dMP2 neuron || embryonic fiber tract || articulation || ventral midline || integumentary specialisation || wing vein L2 || ocellus || ocellar triangle || photoreceptor cell R7 || hindgut || ventral nervous system || vMP2 neuron
Spectrin repeat	0.2767	INHERITED FROM: connective || copper cell || midgut enterocyte || ipsilateral tract || tract || longitudinal connective || middle midgut
vWA-like	0.3389	INHERITED FROM: endocuticular specialization
(Phosphotyrosine protein) phosphatases II	0.3507	INHERITED FROM: intersegmental nerve || lobe system of adult mushroom body || medial lobe of adult mushroom body
Cytochrome P450	0.3822	INHERITED FROM: midgut || larval neuropil glial cell || commissure || embryonic/larval foregut || CNS glial cell || neuropil associated CNS glial cell || midline crossing tract || embryonic/larval hindgut || midline glial cell || larval VNC neuropil glial cell || tract || hindgut || tract neuropil || neuropil glial sheath
HAD-like	0.4126	INHERITED FROM: rhabdomere of eye photoreceptor cell
SET domain	0.4531	INHERITED FROM: haltere || metathoracic leg
BAR/IMD domain-like	0.4771	INHERITED FROM: NMJ bouton || neuromuscular junction
dsRNA-binding domain-like	0.4771	INHERITED FROM: adult MBp lineage neuron || antennal lobe projection neuron adPN || uniglomerular antennal lobe projection neuron || mushroom body extrinsic neuron || Kenyon cell || adult MBp lineage clone || antennal lobe projection neuron iPN || unilateral ACT relay interneuron || alpha/beta Kenyon cell || persistent antennal lobe projection neuron || adult antennal lobe projection neuron || projection neuron
Cadherin-like	0.5322	INHERITED FROM: photoreceptor cell R4
TPR-like	0.9685	INHERITED FROM: antennal nerve || adult antennal nerve

Family domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
NF-kappa-B/REL/DORSAL transcription factors, C-terminal domain	0	DIRECT
Third domain of FERM	0	DIRECT
First domain of FERM	0	DIRECT
Plexin repeat	0	DIRECT
Diacylglycerol kinase-like	0	DIRECT
Mob1/phocein	0	DIRECT
L-arabinose binding protein-like	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
Arrestin/Vps26-like	0	DIRECT
Laminin-type module	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
Erythroid transcription factor GATA-1	0	DIRECT
Phosphatidylinositol phosphate kinase IIbeta, PIPK IIbeta	0	DIRECT
Class I glutamine amidotransferases (GAT)	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Synaptotagmin-like (S variant)	0	DIRECT
Transforming growth factor (TGF)-beta	0	DIRECT
PX domain	0	DIRECT
Choline/Carnitine O-acyltransferase	0	DIRECT
MIR domain	0	DIRECT
SMAD MH1 domain	0	DIRECT
cAMP-binding domain	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Phoshoinositide 3-kinase (PI3K) helical domain	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase UCH-L	0	DIRECT
POU-specific domain	0	DIRECT
BC ATP-binding domain-like	0	DIRECT
Sema domain	0	DIRECT
Rel/Dorsal transcription factors, DNA-binding domain	0	DIRECT
Hairy Orange domain	0	DIRECT
Single strand DNA-binding domain, SSB	0	DIRECT
Phosphate binding protein-like	0	DIRECT
Integrin domains	0	DIRECT
Cell cycle control phosphatase, catalytic domain	0	DIRECT
SAP domain	0	DIRECT
BC N-terminal domain-like	0	DIRECT
Extracellular domain of cell surface receptors	0	DIRECT
p120GAP domain-like	0	DIRECT
Fibroblast growth factors (FGF)	0	DIRECT
EF-hand modules in multidomain proteins	0	DIRECT
SPRY domain	0	DIRECT
PurM N-terminal domain-like	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase, UCH	0	DIRECT
Eps15 homology domain (EH domain)	0	DIRECT
Myb/SANT domain	0	DIRECT
Class II glutamine amidotransferases	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
PurM C-terminal domain-like	0	DIRECT
Forkhead DNA-binding domain	0	DIRECT
RNase III catalytic domain-like	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
L27 domain	0	DIRECT
Smc hinge domain	0	DIRECT
Dachshund-homology domain	0	DIRECT
Phoshoinositide 3-kinase (PI3K), catalytic domain	0	DIRECT
Second domain of FERM	0	DIRECT
ARID domain	0	DIRECT
Pepsin-like	0	DIRECT
Serpins	0	DIRECT
Rhomboid-like	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Homeodomain	0.000000000005967	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.00001094	DIRECT
Fibronectin type III	0.0009322	DIRECT
Protein kinases, catalytic subunit	0.003564	INHERITED FROM: synaptic neuropil || photoreceptor cell R8 of pale ommatidium || intestinal stem cell
Classic zinc finger, C2H2	0.005401	INHERITED FROM: region of integument
Nuclear receptor ligand-binding domain	0.01098	INHERITED FROM: synaptic neuropil || central brain || protocerebrum || mushroom body gamma-lobe || supraesophageal ganglion neuron || neuropil || synaptic neuropil block
SH2 domain	0.01231	INHERITED FROM: wing blade || ommatidium || adult peripheral nervous system || midline crossing tract || photoreceptor cell R7
Nuclear receptor	0.02675	INHERITED FROM: synaptic neuropil || mushroom body gamma-lobe || supraesophageal ganglion neuron || synaptic neuropil block
HMG-box	0.04422	INHERITED FROM: wing || adult external thorax
Ngr ectodomain-like	0.06272	INHERITED FROM: abdominal intersegmental nerve || intersegmental nerve branch ISNb of A1-7 || intersegmental nerve of A1-7
Higher-molecular-weight phosphotyrosine protein phosphatases	0.06272	INHERITED FROM: intersegmental nerve
Paired domain	0.06272	INHERITED FROM: EG neuron || RP2 motor neuron || EL neuron
I set domains	0.08605	INHERITED FROM: synaptic neuropil || leg taste bristle chemosensory neuron || adult brain || dendritic arborizing neuron || antennal lobe glomerulus || connective || gustatory receptor neuron || LNv neuron || segmental subdivision of organ system || LN period neuron || s-LNv neuron || synaptic neuropil block || interface glial cell || tract neuropil || neuropil glial sheath
Histone lysine methyltransferases	0.1094	INHERITED FROM: haltere || metathoracic leg
PLC-like (P variant)	0.1094	INHERITED FROM: dorsal multidendritic neuron || dorsal multidendritic neuron ddaC || mesothoracic tergum
Ankyrin repeat	0.134	INHERITED FROM: Johnston organ neuron || ventral multidendritic neuron
Transducin (alpha subunit), insertion domain	0.1898	INHERITED FROM: eo neuron
Toll/Interleukin receptor TIR domain	0.1898	INHERITED FROM: ventral nerve cord
Calponin-homology domain, CH-domain	0.2286	INHERITED FROM: abdominal segmental nerve
SMAD domain	0.2499	INHERITED FROM: wing blade || wing vein || gut section
Spectrin repeat	0.2745	INHERITED FROM: connective || copper cell || midgut enterocyte || ipsilateral tract || tract || longitudinal connective || middle midgut
SAM (sterile alpha motif) domain	0.3376	INHERITED FROM: mesothoracic leg || metatarsus of male prothoracic leg || metatarsus || sex comb || prothoracic metatarsus || prothoracic tarsal segment || prothoracic leg
Cytochrome P450	0.3896	INHERITED FROM: midgut || larval neuropil glial cell || commissure || embryonic/larval foregut || CNS glial cell || neuropil associated CNS glial cell || midline crossing tract || embryonic/larval hindgut || midline glial cell || larval VNC neuropil glial cell || tract || hindgut || tract neuropil || neuropil glial sheath
Cyclin	0.4222	INHERITED FROM: tagmatic subdivision of organ system
Growth factor receptor domain	0.4599	INHERITED FROM: proventriculus || integumentary specialisation || ocellus || ocellar triangle || dorsocentral bristle || hindgut || salivary gland
EGF-type module	0.5915	INHERITED FROM: proventriculus || wing blade || embryonic/larval midgut cell || articulation || hindgut || ventral nervous system || adult external head || adult midgut progenitor cell
Ubiquitin-related	0.5937	INHERITED FROM: mushroom body extrinsic neuron
Cadherin	0.6239	INHERITED FROM: photoreceptor cell R4 || outer photoreceptor cell
G proteins	0.771	INHERITED FROM: wing hair

Trees by TreeVector

A presence/absence matrix is generated using protein domain architecture data for all genomes in SUPERFAMILY. The PAUP software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
RCC1/BLIP-II	0	DIRECT
Cytokine	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
PurM C-terminal domain-like	0	DIRECT
Orange domain-like	0	DIRECT
Sema domain	0	DIRECT
Rhomboid-like	0	DIRECT
Serpins	0	DIRECT
PurM N-terminal domain-like	0	DIRECT
ARID-like	0	DIRECT
Integrin domains	0	DIRECT
TIMP-like	0	DIRECT
PX domain	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
L27 domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Thiamin diphosphate-binding fold (THDP-binding)	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
SAP domain	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
cAMP-binding domain-like	0	DIRECT
Putative DNA-binding domain	0	DIRECT
SAICAR synthase-like	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
PreATP-grasp domain	0	DIRECT
Smc hinge domain	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Mob1/phocein	0	DIRECT
SMAD MH1 domain	0	DIRECT
MIR domain	0	DIRECT
Second domain of FERM	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
Plexin repeat	0	DIRECT
Homeodomain-like	0.0000000001487	DIRECT
beta-beta-alpha zinc fingers	0.000003804	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.000004445	DIRECT
Fibronectin type III	0.0004713	DIRECT
Immunoglobulin	0.002551	INHERITED FROM: abdominal nerve || adult brain || abdominal segmental nerve || connective || antennal lobe glomerulus || leg taste bristle chemosensory neuron || tract neuropil || neuropil glial sheath || LN period neuron || synaptic neuropil || embryonic/larval peripheral nervous system || interface glial cell || LNv neuron || nerve || commissure
Protein kinase-like (PK-like)	0.003998	INHERITED FROM: photoreceptor cell R8 of pale ommatidium || intestinal stem cell || adult midgut epithelium || synaptic neuropil
p53-like transcription factors	0.007932	INHERITED FROM: integumentary process || adult external thorax || mesothoracic tergum
Nuclear receptor ligand-binding domain	0.007932	INHERITED FROM: synaptic neuropil block || mushroom body gamma-lobe || supraesophageal ganglion neuron || protocerebrum || synaptic neuropil || neuropil || central brain
Glucocorticoid receptor-like (DNA-binding domain)	0.00802	INHERITED FROM: region of integument || adult external thorax
SH2 domain	0.008239	INHERITED FROM: midline crossing tract || ommatidium || connective || wing blade || adult peripheral nervous system || photoreceptor cell R7
PH domain-like	0.02584	INHERITED FROM: embryonic foregut
HMG-box	0.03392	INHERITED FROM: wing || adult external thorax
Cystine-knot cytokines	0.05725	INHERITED FROM: stigmatophore || embryonic/larval posterior spiracle || spiracle || embryonic/larval spiracle
EGF/Laminin	0.08701	INHERITED FROM: eye photoreceptor cell stalk || larval caeca region || embryonic/larval midgut cell || adult midgut progenitor cell || wing blade || proventriculus || tendon cell || ventral nervous system || ocellus
Ankyrin repeat	0.09594	INHERITED FROM: Johnston organ neuron
GTPase activation domain, GAP	0.1293	INHERITED FROM: abdominal intersegmental nerve
Snake toxin-like	0.1721	INHERITED FROM: wing cell || adult optic lobe || wing vein || embryonic/larval neuromuscular junction
Transducin (alpha subunit), insertion domain	0.1721	INHERITED FROM: eo neuron
Toll/Interleukin receptor TIR domain	0.1721	INHERITED FROM: ventral nerve cord
Calponin-homology domain, CH-domain	0.1958	INHERITED FROM: abdominal segmental nerve
Growth factor receptor domain	0.23	INHERITED FROM: ventral midline || hindgut || wing vein L2 || embryonic/larval midline of ventral nerve cord || vMP2 neuron || wing vein L4 || integumentary specialisation || RP2sib neuron || photoreceptor cell R7 || proventriculus || articulation || retinal pigment cell || dMP2 neuron || fascicle || ventral nervous system || ocellar triangle || surface associated glial cell || ocellus || embryonic fiber tract
Spectrin repeat	0.2465	INHERITED FROM: middle midgut || longitudinal connective || connective || midgut enterocyte || copper cell || tract || ipsilateral tract
vWA-like	0.307	INHERITED FROM: endocuticular specialization
(Phosphotyrosine protein) phosphatases II	0.3187	INHERITED FROM: medial lobe of adult mushroom body || lobe system of adult mushroom body || intersegmental nerve
Cytochrome P450	0.3503	INHERITED FROM: midline crossing tract || larval neuropil glial cell || hindgut || midline glial cell || CNS glial cell || larval VNC neuropil glial cell || tract neuropil || neuropil associated CNS glial cell || neuropil glial sheath || embryonic/larval foregut || tract || midgut || embryonic/larval hindgut || commissure
HAD-like	0.3805	INHERITED FROM: rhabdomere of eye photoreceptor cell
SET domain	0.4215	INHERITED FROM: metathoracic leg || haltere
BAR/IMD domain-like	0.4459	INHERITED FROM: NMJ bouton || neuromuscular junction
dsRNA-binding domain-like	0.4459	INHERITED FROM: uniglomerular antennal lobe projection neuron || alpha/beta Kenyon cell || mushroom body extrinsic neuron || projection neuron || Kenyon cell || adult MBp lineage clone || adult antennal lobe projection neuron || antennal lobe projection neuron iPN || unilateral ACT relay interneuron || persistent antennal lobe projection neuron || adult MBp lineage neuron || antennal lobe projection neuron adPN
Cadherin-like	0.5021	INHERITED FROM: photoreceptor cell R4
TPR-like	0.9624	INHERITED FROM: antennal nerve || adult antennal nerve

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
48371,56112 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
101912,103575 101912 - Sema domain 103575 - Plexin repeat	0	DIRECT
49265,49265 49265 - Fibronectin type III 49265 - Fibronectin type III	0	DIRECT
51045,51045 51045 - WW domain 51045 - WW domain	0	DIRECT
52777,52777 52777 - CoA-dependent acyltransferases 52777 - CoA-dependent acyltransferases	0	DIRECT
52440,56059 52440 - PreATP-grasp domain 56059 - Glutathione synthetase ATP-binding domain-like	0	DIRECT
47031,50729 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
57903,47370 57903 - FYVE/PHD zinc finger 47370 - Bromodomain	0	DIRECT
47459,158457 47459 - HLH, helix-loop-helix DNA-binding domain 158457 - Orange domain-like	0	DIRECT
55326,56042 55326 - PurM N-terminal domain-like 56042 - PurM C-terminal domain-like	0	DIRECT
55550,50044 55550 - SH2 domain 50044 - SH3-domain	0	DIRECT
48403,48403 48403 - Ankyrin repeat 48403 - Ankyrin repeat	0	DIRECT
50044,55550 50044 - SH3-domain 55550 - SH2 domain	0	DIRECT
54236,47031 54236 - Ubiquitin-like 47031 - Second domain of FERM	0	DIRECT
49562,48371 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat	0	DIRECT
81660,56784 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like	0	DIRECT
52058,52058 52058 - L domain-like 52058 - L domain-like	0	DIRECT
51206,51206 51206 - cAMP-binding domain-like 51206 - cAMP-binding domain-like	0	DIRECT
47769,47769 47769 - SAM/Pointed domain 47769 - SAM/Pointed domain	0	DIRECT
49417,81296 49417 - p53-like transcription factors 81296 - E set domains	0	DIRECT
57716,48508 57716 - Glucocorticoid receptor-like (DNA-binding domain) 48508 - Nuclear receptor ligand-binding domain	0	DIRECT
49562,49562 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 49562 - C2 domain (Calcium/lipid-binding domain, CaLB)	0	DIRECT
55550,56112 55550 - SH2 domain 56112 - Protein kinase-like (PK-like)	0	DIRECT
47220,47220 47220 - alpha-catenin/vinculin-like 47220 - alpha-catenin/vinculin-like	0	DIRECT
47413,46689 47413 - lambda repressor-like DNA-binding domains 46689 - Homeodomain-like	0	DIRECT
48425,50729 48425 - Sec7 domain 50729 - PH domain-like	0	DIRECT
52058,48726 52058 - L domain-like 48726 - Immunoglobulin	0	DIRECT
57903,57903 57903 - FYVE/PHD zinc finger 57903 - FYVE/PHD zinc finger	0	DIRECT
57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.00001078	DIRECT
48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin	0.02897	INHERITED FROM: synaptic neuropil block || s-LNv neuron || adult deutocerebrum || connective || central nervous system || antennal lobe glomerulus || leg taste bristle chemosensory neuron || tract neuropil || neuropil glial sheath || synaptic neuropil || LNv neuron
48726,49265 48726 - Immunoglobulin 49265 - Fibronectin type III	0.06704	INHERITED FROM: s-LNv neuron || lobe system of adult mushroom body || connective || antennal lobe glomerulus || adult antennal lobe glomerulus || leg taste bristle chemosensory neuron || tract neuropil || neuropil associated CNS glial cell || neuropil glial sheath || gustatory receptor neuron || giant fiber neuron || LNv neuron
49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0.07127	INHERITED FROM: peripheral nervous system || photoreceptor cell R4
46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat	0.09614	INHERITED FROM: middle midgut || longitudinal connective || connective || midgut enterocyte || tract neuropil || copper cell || tract || adult protocerebrum || ipsilateral tract
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.1721	INHERITED FROM: joint || intersegmental nerve || scutum || integumentary specialisation || inner photoreceptor cell || leg || photoreceptor cell R7 || wing vein || proventriculus || articulation || wing blade dorsal compartment
47895,52540 47895 - Transducin (alpha subunit), insertion domain 52540 - P-loop containing nucleoside triphosphate hydrolases	0.1721	INHERITED FROM: eo neuron
47459,55785 47459 - HLH, helix-loop-helix DNA-binding domain 55785 - PYP-like sensor domain (PAS domain)	0.1721	INHERITED FROM: sclerite
81296,81296 81296 - E set domains 81296 - E set domains	0.2324	INHERITED FROM: abdominal nerve || intersegmental nerve || abdominal segmental nerve || segmental nerve || abdominal intersegmental nerve
50156,50044 50156 - PDZ domain-like 50044 - SH3-domain	0.31	INHERITED FROM: embryonic/larval peripheral nervous system
52799,52799 52799 - (Phosphotyrosine protein) phosphatases II 52799 - (Phosphotyrosine protein) phosphatases II	0.31	INHERITED FROM: abdominal nerve || intersegmental nerve || abdominal segmental nerve || segmental nerve || embryonic/larval peripheral nervous system || nerve
57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin	0.3468	INHERITED FROM: eye photoreceptor cell stalk || postfrons || joint || frons || proventriculus || tertiary pigment cell || secondary pigment cell || articulation || ventral nervous system || intersegmental nerve branch ISNb of A1-7 || ocellus || wing blade dorsal compartment
57184,57196 57184 - Growth factor receptor domain 57196 - EGF/Laminin	0.3831	INHERITED FROM: integumentary specialisation
49313,49313 49313 - Cadherin-like 49313 - Cadherin-like	0.5907	INHERITED FROM: wing hair || outer photoreceptor cell || photoreceptor cell R4

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
49562,48371,56112 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
49899,49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
81296,81296,81296 81296 - E set domains 81296 - E set domains 81296 - E set domains	0	DIRECT
81660,56784,81665 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like 81665 - Calcium ATPase, transmembrane domain M	0	DIRECT
52058,52058,52058 52058 - L domain-like 52058 - L domain-like 52058 - L domain-like	0	DIRECT
46966,46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat 46966 - Spectrin repeat	0	DIRECT
57196,49899,49899 57196 - EGF/Laminin 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
54236,47031,50729 54236 - Ubiquitin-like 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
57667,57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.000176	DIRECT
57196,57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin 57196 - EGF/Laminin	0.1209	INHERITED FROM: eye photoreceptor cell stalk || photoreceptor cell R1 || photoreceptor cell R6 || postfrons || adult external head || joint || adult peripheral nervous system || frons || proventriculus || tertiary pigment cell || secondary pigment cell || articulation || ventral nervous system || ocellar triangle || ocellus || wing blade dorsal compartment
48726,48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin 48726 - Immunoglobulin	0.1211	INHERITED FROM: s-LNv neuron || lobe system of adult mushroom body || adult deutocerebrum || connective || leg taste bristle chemosensory neuron || tract neuropil || gustatory receptor neuron || synaptic neuropil || LNv neuron || commissure
48726,48726,49265 48726 - Immunoglobulin 48726 - Immunoglobulin 49265 - Fibronectin type III	0.1293	INHERITED FROM: embryonic/larval central nervous system || s-LNv neuron || lobe system of adult mushroom body || connective || antennal lobe glomerulus || adult antennal lobe glomerulus || leg taste bristle chemosensory neuron || tract neuropil || neuropil associated CNS glial cell || neuropil glial sheath || gustatory receptor neuron || giant fiber neuron || LNv neuron
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.2324	INHERITED FROM: intersegmental nerve || tergum || scutum || integumentary specialisation || adult external mesothorax || dorsal mesothorax || mesothoracic tergum || nerve
49313,49313,49313 49313 - Cadherin-like 49313 - Cadherin-like 49313 - Cadherin-like	0.5907	INHERITED FROM: wing hair || outer photoreceptor cell || photoreceptor cell R4

Trees by TreeVector

A presence/absence matrix is generated using protein domains and supradomains for all genomes in SUPERFAMILY. The RAxML software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.